Beta-lactamase inhibitors are substrates for the multidrug efflux pumps of Pseudomonas aeruginosa.

Antimicrobial Agents and Chemotherapy
X Z LiKeith Poole

Abstract

The MexAB-OprM multidrug efflux system exports a number of antimicrobial compounds, including beta-lactams. In an attempt to define more fully the range of antimicrobial compounds exported by this system, and, in particular, to determine whether beta-lactamase inhibitors were also accommodated by the MexAB-OprM pump, the influence of pump status (its presence or absence) on the intrinsic antibacterial activities of these compounds and on their abilities to enhance beta-lactam susceptibility in intact cells was assessed. MIC determinations clearly demonstrated that all three compounds tested, clavulanate, cloxacillin, and BRL42715, were accommodated by the pump. Moreover, by using beta-lactams which were readily hydrolyzed by the Pseudomonas aeruginosa class C chromosomal beta-lactamase, it was demonstrated that elimination of the mexAB-oprM-encoded efflux system greatly enhanced the abilities of cloxacillin and BRL42715 (but not clavulanate) to increase beta-lactam susceptibility. With beta-lactams which were poorly hydrolyzed, however, the inhibitors failed to enhance beta-lactam susceptibility in MexAB-OprM+ strains, although BRL42715 did enhance beta-lactam susceptibility in MexAB-OprM- strains, suggesting that even with poo...Continue Reading

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
Sep 1, 1992·Antimicrobial Agents and Chemotherapy·N Masuda, S Ohya
Jan 1, 1991·Antibiotics and Chemotherapy·D M Livermore
Sep 1, 1990·Antimicrobial Agents and Chemotherapy·H FukudaS Iyobe
Nov 1, 1989·Antimicrobial Agents and Chemotherapy·H Nikaido
Jun 1, 1995·Antimicrobial Agents and Chemotherapy·K BushA A Medeiros
Mar 1, 1995·Antimicrobial Agents and Chemotherapy·N MasudaS Ohya
Dec 1, 1994·Trends in Microbiology·D MaH Nikaido
Jan 1, 1993·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·I Phillips, K Shannon
Sep 1, 1995·Antimicrobial Agents and Chemotherapy·X Z LiK Poole
Oct 1, 1996·Journal of Bacteriology·H Nikaido
Oct 1, 1996·Antimicrobial Agents and Chemotherapy·T KöhlerJ C Pechere
Aug 1, 1953·The Biochemical Journal·M DIXON

❮ Previous
Next ❯

Citations

Feb 19, 2000·Antimicrobial Agents and Chemotherapy·A BroounK Lewis
Mar 5, 2009·Antimicrobial Agents and Chemotherapy·Lucie VettorettiCatherine Llanes
Feb 27, 2003·Antimicrobial Agents and Chemotherapy·Charles R DeanPatricia A Bradford
Sep 18, 2002·Antimicrobial Agents and Chemotherapy·George TegosKim Lewis
Jan 18, 2002·Antimicrobial Agents and Chemotherapy·Xian-Zhi LiKeith Poole
May 14, 2008·Antimicrobial Agents and Chemotherapy·George P TegosMichael R Hamblin
Oct 2, 2002·European Journal of Biochemistry·Eisaku YoshiharaKohjiro Saito
Mar 20, 2015·Clinical Microbiology Reviews·Xian-Zhi LiHiroshi Nikaido
Jul 19, 2001·Bioorganic & Medicinal Chemistry Letters·A ThorarensenB H Yagi
Aug 11, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Malcolm G. P. Page
May 23, 2015·Frontiers in Microbiology·Timothy J Opperman, Son T Nguyen
Jun 11, 2015·Microbial Biotechnology·Carlos Molina-SantiagoJuan-Luis Ramos
May 30, 2002·The Journal of Biological Chemistry·Daniel LimNatalie C J Strynadka
Nov 20, 2013·Antimicrobial Agents and Chemotherapy·Timothy J OppermanTerry L Bowlin
Jan 5, 2010·The Tohoku Journal of Experimental Medicine·Yoichi HirakataMitsuo Kaku
Jan 26, 2010·American Journal of Respiratory Cell and Molecular Biology·Peter G BarlowDonald J Davidson
Jun 27, 2014·World Journal of Microbiology & Biotechnology·Huseyin Agah TerziIhsan Hakkı Ciftci
May 21, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Judy GopalHui-Fen Wu
Sep 8, 1999·Microbiology and Molecular Biology Reviews : MMBR·H L RocchettaJ S Lam
Dec 6, 2006·Antimicrobial Agents and Chemotherapy·Ying Ying ChanKim Lee Chua
Apr 9, 2001·The Journal of Pharmacy and Pharmacology·K Poole

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Beta-lactamase Inhibitors (ASM)

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Beta-lactamase Inhibitors

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.